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Background and ObjectivesThe multiple sclerosis (MS) population's survival from breast cancer and colorectal cancer is compromised. Cancer screening and timely diagnoses affect cancer survival and have not been studied in the MS cancer population. We investigated whether the diagnostic route, cancer stage, or diagnostic interval differed in patients with cancer with and without MS.MethodsWe conducted a matched population-based cross-sectional study of breast cancers (2007–2015) and colorectal cancers (2009–2012) in patients with MS from Ontario, Canada, using administrative data. Exclusion criteria included second or concurrent primary cancers, no health care coverage, and, for the patients without MS, those with any demyelinating disease. We based 1:4 matching of MS to non-MS on birth year, sex (colorectal only), postal code, and cancer diagnosis year (breast only). Cancer outcomes were diagnostic route (screen-detected vs symptomatic), stage (stage I vs all others), and diagnostic interval (time from first presentation to diagnosis). Multivariable regression analyses controlled for age, sex (colorectal only), diagnosis year, income quintile, urban/rural residence, and comorbidity.ResultsWe included 351 patients with MS and breast cancer, 1,404 matched patients with breast cancer without MS, 54 patients with MS and colorectal cancer, and 216 matched patients with colorectal cancer without MS. MS was associated with fewer screen-detected cancers in breast (odds ratio [OR] 0.68 [95% CI 0.52, 0.88]) and possibly colorectal (0.52 [0.21, 1.28]) cancer. MS was not associated with differences in breast cancer stage at diagnosis (stage I cancer, OR 0.81 [0.64, 1.04]). MS was associated with greater odds of stage I colorectal cancer (OR 2.11 [1.03, 4.30]). The median length of the diagnostic interval did not vary between people with and without MS in either the breast or colorectal cancer cohorts. Controlling for disability status attenuated some findings.DiscussionBreast cancers were less likely to be detected through screening and colorectal cancer more likely to be detected at early stage in people with MS than without MS. MS-related disability may prevent people from getting mammograms and colonoscopies. Understanding the pathways to earlier detection in both cancers is critical to developing and planning interventions to ameliorate outcomes for people with MS and cancer.

Background and ObjectivesWe tested the hypothesis that overall and cancer-specific survival after a colorectal cancer diagnosis is lower in persons with multiple sclerosis (MS) than in those without MS using a retrospective matched cohort design.MethodsUsing population-based administrative data in Manitoba and Ontario, we identified persons with MS from a validated case definition and linked these cohorts to cancer registries to identify those with colorectal cancer. We selected persons with colorectal cancer and without MS, matching 4:1 on birth year, sex, cancer diagnosis year, and region. We used Cox proportional hazards regression to compare all-cause survival between cohorts, adjusting for age at cancer diagnosis, cancer diagnosis year, income, region, and Elixhauser comorbidity score. We compared cancer-specific survival between cohorts using a cause-specific hazards model. We pooled findings across provinces using random-effects meta-analysis. Complementary analyses using a subcohort from Ontario, adjusted for cancer stage and disability status, as measured from the use of home care or long-term care services.ResultsWe included 338 MS cases and 1,352 controls with colorectal cancer. The mean (SD) age at cancer diagnosis was 64.7 (11.1) years. After adjustment, MS was associated with an increased hazard for all-cause death that was highest 6 months after diagnosis (hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.19–1.76) and then declined over time (HR [95% CI] at 1 year 1.34 [1.09–1.63], 2 years 1.24 [0.99–1.56], 5 years 1.10 [0.80–1.50]). MS was associated with increased cancer-specific death at 6 months after diagnosis only (HR 1.29, 95% CI 1.04–1.61). After adjustment for cancer stage, MS was associated with an increased hazard of death due to any cause (1.60, 95% CI 1.16–2.21) and with cancer-specific death (HR 1.47, 95% CI 1.02–2.12). The association of MS and all-cause death was partially attenuated after adjustment for disability status (HR 1.37, 95% CI 0.97–1.92), as was the association with cancer-specific death (HR 1.34, 95% CI 0.91–1.97).DiscussionOverall and cancer-specific survival was lower in persons with than without MS in the early period after colorectal cancer diagnosis. Further study is warranted to determine what factors underlie these worse outcomes.

ObjectiveTo test the hypotheses that overall survival and cancer-specific survival after breast cancer diagnosis would be lower in persons with multiple sclerosis (MS) as compared to persons without MS using a retrospective matched cohort design.MethodsWe applied a validated case definition to population-based administrative data in Manitoba and Ontario, Canada, to identify women with MS. We linked the MS cohorts to cancer registries to identify women with breast cancer. Then we selected 4 breast cancer controls without MS matched on birth year, cancer diagnosis year, and region. We compared all-cause survival between cohorts using Cox proportional hazards regression adjusting for age at cancer diagnosis, cancer diagnosis period, income quintile, region, and Elixhauser comorbidity score. We compared cancer-specific survival between cohorts using a multivariable cause-specific hazards model. We pooled findings between provinces using meta-analysis.ResultsWe included 779 patients with MS and 3,116 controls with breast cancer. Most patients with stage data (1,976/2,822 [70.0%]) were diagnosed with stage I or II breast cancer and the mean (SD) age at diagnosis was 57.8 (10.7) years. After adjustment for covariates, MS was associated with a 28% increased hazard for all-cause mortality (hazard ratio [HR] 1.28; 95% confidence interval [CI] 1.08–1.53), but was not associated with altered cancer-specific survival (HR 0.98; 95% CI 0.65–1.46).ConclusionWomen with MS have lower all-cause survival after breast cancer diagnosis than women without MS. Future studies should confirm these findings in other populations and identify MS-specific factors associated with worse prognosis.

ObjectiveTo determine whether cancer risk differs in people with and without multiple sclerosis (MS), we compared incidence rates and cancer-specific mortality rates in MS and matched cohorts using population-based data sources.MethodsWe conducted a retrospective matched cohort study using population-based administrative data from Manitoba and Ontario, Canada. We applied a validated case definition to identify MS cases, then selected 5 controls without MS matched on birth year, sex, and region. We linked these cohorts to cancer registries, and estimated incidence of breast, colorectal, and 13 other cancers. For breast and colorectal cancers, we constructed Cox models adjusting for age at the index date, area-level socioeconomic status, region, birth cohort year, and comorbidity. We pooled findings across provinces using meta-analysis.ResultsWe included 53,983 MS cases and 269,915 controls. Multivariable analyses showed no difference in breast cancer risk (pooled hazard ratio [HR] 0.92 [95% confidence interval (CI) 0.78–1.09]) or colorectal cancer risk (pooled HR 0.83 [95% CI 0.64–1.07]) between the cohorts. Mortality rates for breast and colorectal did not differ between cohorts. Bladder cancer incidence and mortality rates were higher among the MS cohort. Although the incidence of prostate, uterine, and CNS cancers differed between the MS and matched cohorts, mortality rates did not.ConclusionThe incidence of breast and colorectal cancers does not differ between persons with and without MS; however, the incidence of bladder cancer is increased. Reported differences in the incidence of some cancers in the MS population may reflect ascertainment differences rather than true differences.

ObjectiveWe compared the prevalence of physical and mental conditions and rate of health care utilization in mothers of children with multiple sclerosis (MS) (MS-mothers) with that of mothers of children without MS (non-MS-mothers).MethodsUsing population-based administrative data from Ontario, Canada, we identified MS-mothers and non-MS-mothers, matched on maternal age at childbirth, region, and the child's age and sex at the time of MS diagnosis. We compared the prevalence of any physical condition or any mood or anxiety disorder between the cohorts, in the child's MS diagnosis year, and 5 years before and after diagnosis. We compared rates of physician visits before diagnosis, during the diagnosis year, and after the child's diagnosis using multivariable regression models with generalized estimating equations adjusting for maternal age, socioeconomic status, region of residence, and index year.ResultsWe identified 156 MS-mothers and 624 non-MS-mothers. MS-mothers had a higher prevalence of any physical condition and of any mood or anxiety disorder than non-MS-mothers, before, during, and after their child's diagnosis. On multivariable analysis, MS-mothers did not have higher rates of primary care visits (rate ratio [RR] 1.04; 95% confidence interval [CI] 0.90–1.20), but exhibited increased odds of having any psychiatry visits (odds ratio 1.60; 95% CI 1.10–2.31); the rate of visits did not differ when they did occur (RR 0.66; 95% CI 0.33–1.30).ConclusionMothers of children with MS use more mental health services before and after their child's MS diagnosis than mothers of children without MS. Pediatric health care providers should consider the mental well-being of mothers and their children with MS.

Background: Migration studies may provide insights into environmental determinants of multiple sclerosis (MS) and whether a critical window for exposure exists. We aimed to determine risk factors for MS in immigrants and compare MS risk in immigrants versus long-term residents in Ontario, Canada. Methods: We applied a validated algorithm to linked, population-based immigration and health claims data to identify incident MS cases in immigrants and long term-residents between 1994 and 2016. We conducted two multivariable Cox proportional hazards regression analyses including one limited to the immigrant cohort assessing potential risk factors for developing MS; and one comparing MS risk between immigrants and matched long-term residents (1:3 match). Results: We identified 2,304,302 immigrants for the immigrant-only analysis, of whom 1,526 (0.066%) developed MS. Younger age at migration, female sex, greater co-morbidity burden, lower neighbourhood income, and time since landing were associated with increased MS risk. Risk was greatest in those

Background and ObjectivesLittle is known about the effect of education or other indicators of cognitive reserve on the rate of reversion from mild cognitive impairment (MCI) to normal cognition (NC) or the relative rate (RR) of reversion from MCI to NC vs progression from MCI to dementia. Our objectives were to (1) estimate transition rates from MCI to NC and dementia and (2) determine the effect of age,APOE, and indicators of cognitive reserve on the RR of reversion vs progression using multistate Markov modeling.MethodsWe estimated instantaneous transition rates between NC, MCI, and dementia after accounting for transition to death across up to 12 assessments in the Nun Study, a cohort study of religious sisters aged 75+ years. We estimated RRs of reversion vs progression for age,APOE, and potential cognitive reserve indicators: education, academic performance (high school grades), and written language skills (idea density, grammatical complexity).ResultsOf the 619 participants, 472 were assessed with MCI during the study period. Of these 472, 143 (30.3%) experienced at least one reverse transition to NC, and 120 of the 143 (83.9%) never developed dementia (mean follow-up = 8.6 years). In models adjusted for age group andAPOE, higher levels of education more than doubled the RR ratio of reversion vs progression. Novel cognitive reserve indicators were significantly associated with a higher adjusted RR of reversion vs progression (higher vs lower levels for English grades: RR ratio = 1.83; idea density: RR ratio = 3.93; and grammatical complexity: RR ratio = 5.78).DiscussionKnowledge of frequent reversion from MCI to NC may alleviate concerns of inevitable cognitive decline in those with MCI. Identification of characteristics predicting the rate of reversion from MCI to NC vs progression from MCI to dementia may guide population-level interventions targeting these characteristics to prevent or postpone MCI and dementia. Research on cognitive trajectories would benefit from incorporating predictors of reverse transitions and competing events, such as death, into statistical modeling. These results may inform the design and interpretation of MCI clinical trials, given that a substantial proportion of participants may experience improvement without intervention.

Objective: To estimate the prevalence of depression in persons with epilepsy (PWE) and the strength of association between these 2 conditions. Methods: The MEDLINE (1948–2012), EMBASE (1980–2012), and PsycINFO (1806–2012) databases, reference lists of retrieved articles, and conference abstracts were searched. Content experts were also consulted. Two independent reviewers screened abstracts and extracted data. For inclusion, studies were population-based, original research, and reported on epilepsy and depression. Estimates of depression prevalence among PWE and of the association between epilepsy and depression (estimated with reported odds ratios [ORs]) are provided. Results: Of 7,106 abstracts screened, 23 articles reported on 14 unique data sources. Nine studies reported on 29,891 PWE who had an overall prevalence of active (current or past-year) depression of 23.1% (95% confidence interval [CI] 20.6%–28.31%). Five of the 14 studies reported on 1,217,024 participants with an overall OR of active depression of 2.77 (95% CI 2.09–3.67) in PWE. For lifetime depression, 4 studies reported on 5,454 PWE, with an overall prevalence of 13.0% (95% CI 5.1–33.1), and 3 studies reported on 4,195 participants with an overall OR of 2.20 (95% CI 1.07–4.51) for PWE. Conclusions: Epilepsy was significantly associated with depression and depression was observed to be highly prevalent in PWE. These findings highlight the importance of proper identification and management of depression in PWE.